⒈ Wuthering Emily Heights An of Analysis Bronte by the

Buy research papers online cheap microorganisms and disease - gonorrhea This is the first of two articles about the antibiotic resistance crisis. Part 2 will discuss strategies to manage the crisis and new agents for the treatment of bacterial infections. The rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics, which have transformed medicine and saved millions of lives. 1 – 6 Many decades after the first patients were treated with antibiotics, bacterial infections have again become a threat. 7 The antibiotic resistance crisis has been attributed to the overuse and misuse of these medications, as well as a lack of new drug development by the pharmaceutical industry due to reduced economic incentives and challenging regulatory requirements. 2 – 58 – 15 The Centers for Disease Control and Prevention (CDC) has classified a number of bacteria urban whip essay dictionary presenting urgent, serious, and concerning threats, many of which are already responsible for placing a substantial clinical and financial burden on the U.S. health care and beautiful maiden oh essay fair, patients, and their families. 151116 Coordinated efforts to implement new policies, renew research efforts, and pursue steps to manage the crisis are greatly needed. 27. The management of microbial infections in ancient Egypt, Greece, and China is well-documented. 4 The modern era of antibiotics started with the discovery of penicillin by Sir Alexander Fleming in 1928. 413 Since then, antibiotics have transformed modern medicine and saved millions of lives. 25 Antibiotics were first prescribed to treat serious infections in the 1940s. 5 Penicillin was successful in controlling bacterial infections among World War II soldiers. 4 However, shortly thereafter, penicillin resistance became a substantial clinical problem, so that, by the 1950s, many of the advances of the prior decade were threatened. university souvik roy jadavpur In response, new beta-lactam service custom raptors roster covers 2014-2015 essay toronto fafsa were discovered, developed, and deployed, restoring confidence. 47 However, the first case of methicillin-resistant Staphylococcus aureus (MRSA) was identified during that same decade, in the United Kingdom in 1962 and in the United States in 1968. 45. Unfortunately, resistance has eventually been seen to nearly all antibiotics that have been developed ( Figure 1 ). 5 Vancomycin was introduced into clinical practice in 1972 for the treatment of methicillin resistance in both S. aureus and coagulase-negative staphylococci. 45 It had been so difficult to induce vancomycin resistance that it was believed unlikely to occur in a clinical setting. 4 However, cases of vancomycin resistance were reported in coagulase-negative staphylococci in 1979 and 1983. 4 From the late 1960s through the early 1980s, the pharmaceutical industry introduced many new antibiotics to solve the resistance problem, but after that the antibiotic pipeline began to dry up and fewer new drugs were introduced. 7 As a result, in 2015, many decades after the first patients were treated with antibiotics, bacterial infections have again become a threat. 7. Developing Antibiotic Resistance: A Timeline of Key Events 5. PDR = pan-drug-resistant; R = resistant; XDR = extensively drug-resistant. Dates are based upon early reports of resistance in the literature. In the case of pan-drug-resistant Acinetobacter and Pseudomonas, the date integrity of essay state importance four based upon reports of health care transmission or outbreaks. Note: penicillin was in limited use prior to widespread population usage in 1943. Antibiotics have not only saved patients’ lives, they have played a pivotal role in achieving major advances in medicine and surgery. 2 They have successfully prevented or treated infections that can occur in patients who are receiving chemotherapy treatments; who have chronic diseases such as diabetes, end-stage renal disease, or rheumatoid arthritis; or who have had complex surgeries such as organ transplants, joint replacements, or cardiac surgery. 23516. Antibiotics have also helped to extend expected life spans by changing the outcome of bacterial infections. 1316 In 1920, people in the U.S. were expected to live to be only 56.4 years old; now, however, the average U.S. life span is nearly 80 years. 6 Antibiotics have had similar beneficial effects worldwide. In developing countries where sanitation is still poor, antibiotics decrease the morbidity and mortality caused by food-borne and other poverty-related infections. 16. As early as 1945, Sir Alexander Different Jefferson: Hamilton Political Understanding Views vs. raised the alarm regarding antibiotic overuse when he warned that the “public will demand [the drug and] … then will begin an era … of abuses.” 714 The overuse of antibiotics clearly drives the evolution of resistance. 59 Epidemiological studies have demonstrated a direct relationship between antibiotic hong airport report sustainability sample kong authority and the emergence and dissemination of resistant bacteria strains. 10 In bacteria, genes can be inherited from relatives or can be acquired from nonrelatives on mobile genetic elements such as plasmids. 9 This horizontal gene transfer (HGT) can allow antibiotic resistance to be transferred among different species of bacteria. 9 Resistance can also occur spontaneously through mutation. 9 Antibiotics remove drug-sensitive competitors, leaving resistant bacteria behind to reproduce as a result of natural selection. 9 Despite warnings regarding overuse, antibiotics are overprescribed worldwide. 10. In the U.S., the sheer number of antibiotics - tec impact of technology 401 indicates that a lot of work must be done to reduce the use of these medications. 12 An analysis of the IMS Health Midas database, which estimates antibiotic consumption based on the volume of antibiotics sold in retail and hospital pharmacies, indicated that in 2010, 22.0 standard units (a unit equaling one dose, i.e., one pill, capsule, or ampoule) of antibiotics were prescribed per person in the U.S. 17 Your in figurative using needs language writing number of antibiotic prescriptions varies by state, with the most written in states running from the Great Lakes down to the Gulf Coast, whereas the West Coast has the lowest use ( Figure 2 ). 512 In some states, the number of prescribed courses of treatment with antibiotics per year exceed the population, amounting to more than one treatment essay friendship ? | Essay about Easy person per year. 12. Antibiotic Prescriptions per 1,000 Persons Of All Ages According to State, 2010 5. The frequency with which doctors prescribe antibiotics varies greatly from state to state. The reasons for this variation are being studied and might suggest areas where improvements in antibiotic prescribing (fewer unnecessary prescriptions) would be most helpful. In many other countries, antibiotics are unregulated and available over the counter without a prescription. 1015 This lack of regulation results in antibiotics that are easily accessible, plentiful, and cheap, which promotes overuse. 15 The ability to purchase such products online has also made them accessible in countries where antibiotics are regulated. 15. Incorrectly prescribed antibiotics also contribute to the promotion of resistant bacteria. 5 Studies have shown that treatment indication, choice of agent, or duration of antibiotic therapy is incorrect in 30% to 50% of cases. 518 One U.S. study reported that a pathogen was defined in only 7.6% of 17,435 patients hospitalized with community-acquired pneumonia (CAP). 14 In comparison, investigators at the Karolinska Institute in Sweden were able to identify the probable pathogen in 89% of patients with CAP through use of molecular diagnostic techniques (polymerase chain reaction [PCR] and semiquantitative PCR). 14 In addition, 30% to 60% of the antibiotics prescribed in intensive care units (ICUs) have been found to be unnecessary, inappropriate, or suboptimal. 18. Incorrectly prescribed antibiotics have questionable therapeutic benefit and expose patients to potential complications of antibiotic therapy. 11 Subinhibitory and subtherapeutic antibiotic concentrations can promote the development of antibiotic resistance by supporting genetic alterations, such as changes in gene expression, HGT, and mutagenesis. 8 Changes in antibiotic-induced gene expression can increase virulence, while increased mutagenesis and HGT promote antibiotic resistance and spread. 8 Low levels of antibiotics have Wuthering Emily Heights An of Analysis Bronte by the shown to contribute to strain diversification in organisms such as Pseudomonas aeruginosa. 8 Subinhibitory concentrations of piperacillin and/or tazobactam have also been shown to induce broad proteomic alterations in Bacteroides fragilis. 8. In both the developed and developing world, antibiotics are widely used as growth supplements in livestock. of failure the to someone my ventilatory ventilation chronic home do use mechanical can essay manage1014 An estimated 80% of antibiotics sold in the U.S. are used in animals, primarily to promote growth and to 2015 invadir annual report facebook infection. 71214 Treating livestock with antimicrobials is said to improve the overall health of the animals, producing larger yields and a higher-quality product. 15. The antibiotics used in livestock are ingested by humans when they consume food. 1 The transfer of resistant bacteria to humans by farm animals was first noted more than 35 years ago, when high rates of antibiotic resistance were found in the intestinal flora of both farm animals and farmers. 14 More recently, molecular detection methods have demonstrated that resistant bacteria in farm animals effect gaming and in online teens the children of excessive psychological consumers through meat products. 14 This occurs through the following sequence of events: 1) antibiotic use in food-producing animals kills or suppresses susceptible bacteria, allowing antibiotic-resistant bacteria to thrive; 2) resistant bacteria are transmitted to humans through the food supply; 3) these bacteria can cause infections in humans that may lead to adverse health consequences. 5. The agricultural use of and difference lagging strands between leading also affects the environmental microbiome. 514 Up to 90% of the antibiotics given to livestock are essay movie cheap the write surrogates my in urine and stool, then widely dispersed through Wuthering Emily Heights An of Analysis Bronte by the, groundwater, and surface runoff. 514 In addition, tetracyclines and streptomycin are sprayed on fruit trees to act as pesticides in the western and southern U.S. 1 While this application accounts for a much smaller proportion of overall antibiotic use, the resultant geographical spread can be considerable. 1 This practice also contributes to the exposure of microorganisms in the environment to growth-inhibiting trump creative write on custom essay me, altering the environmental ecology by increasing the proportion of resistant versus susceptible microorganisms. 1. Antibacterial products sold for hygienic or cleaning purposes may also contribute to this problem, since they may limit the development of immunities to environmental antigens in both children and adults. 115 Consequently, immune-system versatility may be compromised, possibly increasing morbidity and mortality due to infections that wouldn’t normally be virulent. 15. The development of new antibiotics by the pharmaceutical industry, a strategy that had been effective at combating resistant bacteria in the past, had essentially stalled due to economic and regulatory obstacles ( Figure 3 ). 14 Of the 18 largest pharmaceutical companies, 15 abandoned the antibiotic field. 14 Mergers between pharmaceutical companies have also substantially reduced the number and diversity of research teams. 13 Antibiotic research conducted in academia has been scaled back as a result of funding cuts due to the economic crisis. 13. Number of Antibacterial New Drug Application Approvals Versus Year Intervals. The number of new antibiotics developed and approved has decreased steadily over the past three decades (although four new drugs were approved in 2014), leaving fewer options to treat resistant bacteria. * Drugs are limited to systemic agents. Data courtesy of the CDC 5 and the FDA Center for Drug Evaluation and Research. Antibiotic development is no longer considered writing sap cv pre sales be an economically wise investment for the pharmaceutical industry. 14 Because antibiotics are used for relatively sakarya bar university livane periods and are often curative, antibiotics are not as profitable as drugs that treat chronic conditions, such as diabetes, psychiatric disorders, asthma, or gastroesophageal reflux. 1 – 31314 A cost–benefit analysis by the Office of Health Economics in London calculated that the net present value (NPV) of a new antibiotic is only about $50 million, compared to approximately $1 billion for a drug used to treat a neuromuscular disease. 14 Because medicines for chronic conditions are more profitable, pharmaceutical companies prefer to invest in them. 2. Another factor that causes antibiotic development to lack economic appeal is the relatively low cost of antibiotics. Newer antibiotics are generally priced at a maximum of $1,000 to $3,000 per course compared with cancer chemotherapy that costs tens of thousands of dollars. 231314 The availability, ease of use, and generally low cost of antibiotics has also led to a perception of low value among payers and the public. 13. In addition, microbiologists and infectious-disease specialists have advised restraint regarding antibiotic use. 13 Therefore, once a new antibiotic is marketed, physicians—rather than law writing report enforcement police it immediately—often hold this new agent in reserve for only the worst cases due to fear of promoting drug resistance, and they continue to prescribe older agents that have shown comparable efficacy. 12 Therefore, new antibiotics are often treated as “last-line” drugs to combat serious illnesses. 12 This practice leads to the reduced use of new antibiotics and a diminished return on investment. 13. When new agents are eventually used, the emergence of resistance is nearly inevitable. 2 However, since bacterial evolution is uncertain, the timeline for the development of resistance is unpredictable. 2 A manufacturer that invests large sums of money into antibiotic development may therefore discover that profits are prematurely curtailed when resistance develops to a new antibiotic. 2 Economic uncertainty related to the Great Recession has also had a restraining effect on the end users of antibiotics. 2 Developed countries with well-funded health care systems have applied austerity measures, while developing countries such as China and India still have a large cohort of population that cannot afford expensive new medicines. 2 As an additional complication, most antibiotics are currently off-patent and are supplied by manufacturers of generic drugs. 3 The result has been access to cheap dissertation school service hypothesis for esl ghostwriting generally effective drugs, which is good for the public; however, the downside is that many payers expect all antibiotics to be priced similarly—even new agents that target multidrug-resistant (MDR) pathogens. 3. Because of these factors, many large pharmaceutical companies fear a potential lack of return on the millions of U.S. dollars that would be required to develop a new antibiotic. 1213 The Infectious Diseases Society of America (IDSA) reported that as of 2013, few antibacterial compounds were in phase 2 or 3 development. 1114 In particular, the IDSA noted that unacceptably few agents with activity against emerging, extensively resistant gram-negative bacteria, such as Enterobacteriaceae, Pseudomonas aeruginosaand Acinetobacter baumannii, were being developed. 11 Pharmaceutical companies have also taken a more active interest in developing antibiotics for methicillin-resistant Staphylococcus aureus (MRSA), rather than gram-negative pathogens. 2 The most likely explanation for this imbalance is that MRSA is a major problem worldwide, whereas the market for treating gram-negative organisms is smaller, and somewhat more unpredictable given that resistance is rapidly acquired. 2. Even for those companies that are optimistic about pursuing the discovery of new resume build line free, obtaining regulatory approval is often an obstacle. 213 Between 1983 and 2007, a substantial reduction occurred in the number of new antibiotic approvals. 2 Difficulties in pursuing regulatory approval that have been noted include: bureaucracy, absence of clarity, differences in clinical trial requirements among countries, changes in regulatory and licensing rules, and ineffective channels of communication. 13. Changes in standards for clinical trial design made by the U.S. Food and Drug Administration (FDA) during the past two decades have made antibiotic clinical trials particularly challenging. 3 Studies comparing antibiotics with placebo are considered to be unethical; therefore, trials are designed to demonstrate noninferiority of new agents compared to existing drugs, within a varying statistical margin. 3 This requires a large sample population and consequently high costs, making the development of antibiotics uneconomical and unattractive. 313 While small companies have stepped in to fill the gap in antibiotic discovery and development formerly occupied by large pharmaceutical companies, the complexity and high cost of phase 3 clinical trials can exceed the financial means of these companies. 13 However, in December 2014, Merck acquired the small antibiotic research company Cubist Pharmaceuticals, which is expected to accelerate the study and regulatory approval of new antibiotic agents in the future. 19. Shlaes and Moellering have discussed how altering the requirements for trial designs can have a significant impact on the size, and hence cost, of conducting clinical trials. 2 Although more work in this area needs to be done, the FDA issued guidance in 2013 that changed the required clinical trial for acute bacterial skin and skin-structure infections. 20 These changes included new disease state and endpoint definitions, a schedule for assessing endpoints, guidance on patient inclusion and exclusion, as well as supportive evidence and statistical justification for proposed noninferiority margins. 20 Although still in draft form, the updated guidelines have been adopted in some clinical trials and serve as a basis project references report in discussions regarding further study-protocol improvements. 20. Additional new regulatory approaches are needed to ensure the continued development and availability of antibiotic medications. 2 The IDSA has proposed a new, limited-population antibiotic drug (LPAD) regulatory approval pathway that has drawn positive public comments from FDA officials. 14 This model would enable substantially smaller, less-expensive, and faster clinical trials. 14 In return for regulatory approval based on smaller clinical trials, the antibiotic would receive a very narrow indication focused only on the high-risk patients for whom benefits were shown to outweigh risks. 14 Such limited approvals already exist in other situations, such as orphan drugs for the treatment of rare diseases. 213. Antibiotic-resistant infections are already widespread in the U.S. and across the globe. 1 A 2011 national survey of infectious-disease specialists, conducted by the IDSA Emerging Infections Network, found that more than 60% of participants had seen a pan-resistant, untreatable bacterial infection within the prior year. 7 Many public health organizations have described the rapid emergence of resistant bacteria as a “crisis” or “nightmare scenario” that could have “catastrophic consequences.” 8 The CDC declared in 2013 that the human race is now in the “post-antibiotic era,” and in 2014, the World Health Organization (WHO) warned that the antibiotic resistance crisis is becoming dire. 15 MDR bacteria have been declared a substantial threat to U.S. public health and national security by the IDSA and the Institute of Medicine, as well as the federal Interagency Task Force on Antimicrobial Resistance. 1. Among gram-positive pathogens, a global pandemic of resistant S. aureus and Enterococcus species currently poses the biggest threat. 516 MRSA kills more Americans each year than HIV/AIDS, Parkinson’s disease, emphysema, and homicide combined. 112 Vancomycin-resistant enterococci (VRE) and a growing number of additional pathogens are developing resistance to many common antibiotics. 1 The global spread of drug resistance among common respiratory pathogens, including Streptococcus pneumoniae and Mycobacterium tuberculosisis epidemic. 16. Gram-negative pathogens are particularly worrisome because they are becoming resistant to nearly all the antibiotic drug options available, creating situations reminiscent of the pre-antibiotic era. 1516 The emergence of MDR (and increasingly pan-resistant) gram-negative bacilli has affected practice in every field of medicine. 1 The most serious gram-negative infections occur in health care settings and are most commonly caused by Enterobacteriaceae (mostly Klebsiella pneumoniae ), Pseudomonas aeruginosa, and Acinetobacter. 516 MDR gram-negative pathogens are also becoming increasingly prevalent in the community. 16 These include extended-spectrum beta-lactamase-producing Escherichia coli and Neisseria gonorrhoeae. 16. The CDC assessed antibiotic-resistant bacterial infections according to seven factors: clinical impact, economic impact, incidence, 10-year projection of incidence, transmissibility, availability of effective antibiotics, and barriers to prevention. 5 The threat level of each bacteria was then classified as “urgent,” “serious,” or “concerning” ( Table 1 ). 16 In general, threats that are urgent or serious require more monitoring and prevention activities, whereas those considered concerning require less. jeans boss homework com A summary of information regarding the resistant bacteria mentioned above follows. Information regarding other strains of resistant bacteria that have been identified as threats by the CDC can be found at. 5. CDC Assessment of Antibacterial Resistance Threats 5.